USP Standards

Pharmacopeial Standards Governing Compounding

United States Pharmacopeia (USP) standards are the core regulatory and quality benchmarks for pharmacy compounding. They ensure that medications prepared in pharmacies are safe, effective, and free from contamination. For the PTCE and other pharmacy technician exams, understanding the differences between USP chapters <795> (Nonsterile Compounding), <797> (Sterile Compounding), and <800> (Hazardous Drug Handling) is critical. These standards dictate everything from air quality and garbing procedures to beyond-use dates (BUDs). Violating these standards can lead to patient harm, product recalls, and loss of pharmacy licensure. ^[1]

ISO Cleanroom Classifications and Engineering Controls

• United States Pharmacopeia (USP): The official public standards-setting authority for all prescription and over-the-counter medicines manufactured or sold in the U.S. ^[2]
• National Formulary (NF): A companion to the USP that sets standards for excipients and other pharmaceutical ingredients.
• ISO Classification: A measure of air cleanliness based on the maximum number of particles allowed per cubic meter.
  • ISO Class 5: Required for Primary Engineering Controls (PECs) like laminar airflow workbenches (LAFWs) and compounding aseptic isolators (CAIs).
  • ISO Class 7: Required for the Buffer Room (cleanroom) surrounding the PEC.
  • ISO Class 8: Minimum requirement for the Ante Room (Anteroom).
• Primary Engineering Control (PEC): The device where sterile compounding occurs (e.g., LAFW, CAI, Biological Safety Cabinet).
• Secondary Engineering Control (SEC): The room (Buffer Room) that houses the PEC.
• Ante Room (Anteroom): A transition area where personnel perform hand hygiene, garbing, and staging of supplies. It separates the Buffer Room from the general pharmacy.
• Beyond-Use Date (BUD): The date or time after which a compounded preparation should not be used. It is based on sterility and stability data.
• First Air: The uncontaminated air from the HEPA filter that flows toward the product. Nothing should obstruct this path. ^[3]

Comparison of USP Compounding Chapters

Nonsterile, Sterile, and Hazardous Compounding Procedures

1. Nonsterile Compounding (USP <795>)

This covers the preparation of nonsterile products (e.g., ointments, capsules, suspensions). The technician must ensure accuracy and homogeneity.

1. Identify the correct ingredients and calculate the quantities needed.
2. Calibrate the compounding equipment (balance, mortar and pestle).
3. Document the master formula and batch record.
4. Compound using proper geometric dilution for triturations.
5. Assign a BUD based on the chapter guidelines (usually 90 days for nonsterile oral formulations unless otherwise specified).

2. Sterile Compounding (USP <797>)

This is high-risk due to the potential for microbial contamination. Strict adherence to aseptic technique is required.

Personnel Garbing Sequence (Clean to Dirty)

1. Remove personal outerwear and jewelry.
2. Don shoe covers or dedicated shoes.
3. Don a head cover (hair net) and a face mask (must cover beards).
4. Perform hand hygiene (scrub for 30 seconds with non-antimicrobial soap).
5. Don a sterile, non-shedding gown.
6. Enter the Ante Room (ISO 8). Perform waterless alcohol-based hand rub (15 seconds).
7. Don sterile powder-free gloves.
8. Enter the Buffer Room (ISO 7). Sanitize gloves with sterile 70% IPA before entering the PEC.

Aseptic Technique

• Always work at least 6 inches inside the PEC.
• Never obstruct the First Air pathway.
• Swab vial diaphragms with sterile 70% IPA and allow them to dry.
• Use a “no-touch” technique when handling needles and syringes.
• Perform a gloved fingertip test (at least annually, but initially before allowed to compound) to ensure aseptic technique competency. ^[4]

3. Hazardous Drug Compounding (USP <800>)

• Requires a Biological Safety Cabinet (BSC) or a Compounding Aseptic Isolator (CACI) for containment.
• The room must have negative pressure relative to the surrounding areas to prevent hazardous particles from escaping.
• A Closed-System Transfer Device (CSTD) must be used during compounding.
• All waste from hazardous drug compounding (gloves, gowns, vials, IV bags) must be disposed of in a yellow chemotherapy waste container.

Cleanroom Environmental Monitoring and Personnel Sampling

Environmental monitoring is essential to verify that the compounding environment meets USP standards.

• Viable Air Sampling: Uses settling plates or volumetric samplers to detect microbial growth. Performed at least every 6 months (quarterly for high-risk).
• Non-Viable Particulate Counting: Measures the number of airborne particles. Performed annually or after any construction.
• Gloved Fingertip Sampling: Directly tests the gloves of the compounding personnel for bacteria. Must be performed at least annually, and initially before an individual is allowed to compound sterile products.
• Surface Sampling: Contact plates are pressed onto surfaces (e.g., inside the PEC, countertops) to check for contamination.

Patient and Staff Safety Hazards in Compounding

• Patient Safety:
  • Microbial Contamination: Can lead to sepsis, pyrogenic reactions (fever) or death.
  • Particulate Matter: Glass shards or fibers can cause phlebitis or embolism.
  • Air Embolism: Introduced by improper IV line priming or syringe technique.
  • Wrong Dose/Medication: Caused by mislabeling or miscalculation.
• Staff Safety:
  • Hazardous Drug Exposure: Can cause reproductive harm, cancer, or organ toxicity. Always use CSTDs and proper PPE.
  • Needlestick Injuries: Always dispose of needles immediately into a sharps container without recapping.
  • Latex Allergies: Use non-latex gloves if allergic.

Critical Recall Items for Compounding Certification

• Memorize the ISO classifications: PEC (ISO 5), Buffer Room (ISO 7), Ante Room (ISO 8).
• Know your BUDs: Nonsterile (usually 90 days), Sterile Low-Risk (48 hours at room temp, 14 days refrigerated), Sterile High-Risk (24 hours at room temp, 3 days refrigerated).
• Garbing Order: Head cover → Beard cover (if applicable) → Face mask → Hand wash → Gown → Alcohol hand rub → Gloves → Sanitize gloves.
• First Air is a favorite exam concept. If an object is placed directly in the path of unidirectional airflow, the object is no longer sterile.
• Perfect 6-inch rule: Always work at least 6 inches inside the hood.
• Glove fingertip testing: Must be done initially before compounding, and at least annually thereafter.
• Isolator vs. LAFW vs. BSC: LAFW (horizontal flow) for non-hazardous. BSC (vertical flow, negative pressure) for hazardous.

References & Sources

1. United States Pharmacopeia (USP). "USP General Chapter <795>: Pharmaceutical Compounding—Nonsterile Preparations." USP-NF. https://www.usp.org/events-training/course/usp-general-chapter-795-pharmaceutical-compounding-nonsterile-preparations-1
2. United States Pharmacopeia (USP). "USP General Chapter <797>: Pharmaceutical Compounding—Sterile Preparations." USP-NF. https://www.usp.org/events-training/course/usp-general-chapter-797-pharmaceutical-compounding-sterile-preparations-0
3. United States Pharmacopeia (USP). "USP General Chapter <800>: Hazardous Drugs—Handling in Healthcare Settings." USP-NF. https://www.usp.org/events-training/course/usp-general-chapter-800-hazardous-drugs-handling-healthcare-settings-demand
4. Centers for Disease Control and Prevention (CDC). "Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for Safe Care." CDC Guidelines. https://www.cdc.gov/healthcare-associated-infections/hcp/prevention-healthcare/outpatient-expectations.html
5. Mizner, J. (Ed.). (2021). Mosby's Pharmacy Technician: Principles and Practice (5th ed.). Elsevier. ISBN: 978-0323550482. https://shop.elsevier.com/books/mosbys-pharmacy-technician/elsevier-inc/978-0-323-44356-2